CuII Pyrazolyl-Benzimidazole Dinuclear Complexes with Remarkable Antioxidant Activity.

Three dinuclear coordination complexes generated from 1-n-butyl-2-((5-methyl-1H-pyrazole-3-yl)methyl)-1H-benzimidazole (L), have been synthesized and characterized spectroscopically and structurally by single crystal X-ray diffraction analysis. Reaction with iron(II) chloride and then copper(II) nitrate led to a co-crystal containing 78 % of [Cu(NO3 )(µ-Cl)(L')]2 (C1 ) and 22 % of [Cu(NO3 )(µ-NO3 )(L')]2 (C2 ), where L was oxidized to a new ligand L' . A mechanism is provided. Reaction with copper chloride led to the dinuclear complex [Cu(Cl)(µ-Cl)(L)]2 (C3 ). The presence of N-H⋅⋅⋅O and C-H⋅⋅⋅O intermolecular interactions in the crystal structure of C1 and C2 , and C-H⋅⋅⋅N and C-H⋅⋅⋅Cl hydrogen bonding in the crystal structure of C3 led to supramolecular structures that were confirmed by Hirshfeld surface analysis. The ligands and their complexes were tested for free radical scavenging activity and ferric reducing antioxidant power. The complex C1 /C2 shows remarkable antioxidant activities as compared to the ligand L and reference compounds.

Assessment of anti-hyperglycemic and anti-hyperlipidemic effects of thiazolidine-2,4-dione derivatives in HFD-STZ diabetic animal model.

Type 2 diabetes mellitus (T2DM) is a chronic endocrine/metabolic disorder characterized by elevated postprandial and fasting glycemic levels that result in disturbances in primary metabolism. In this study, we evaluated the metabolic effects of thiazolidine-2,4-dione derivatives in Wistar rats and Swiss mice that were fed a high-fat diet (HFD) for 4 weeks and received 90 mg/kg of streptozotocin (STZ) intraperitoneally as a T2DM model. The HFD consisted of 17% carbohydrate, 58% fat, and 25% protein, as a percentage of total kcal. The thiazolidine-2,4-dione derivatives treatments reduced fasting blood glucose (FBG) levels by an average of 23.98%-50.84%, which were also improved during the oral starch tolerance test (OSTT). Treatment with thiazolidine-2,4-dione derivatives also improved triglyceride (TG), low-density lipoprotein cholesterol (LDL-c), and total cholesterol levels (P < 0.05). The treatment intake has also shown a significant effect to modulate the altered hepatic and renal biomarkers. Further treatment with thiazolidine-2,4-dione derivatives for 28 days significantly ameliorated changes in appearance and metabolic risk factors, including favorable changes in histopathology of the liver, kidney, and pancreas compared with the HFD/STZ-treated group, suggesting its potential role in the management of diabetes. Thiazolidine-2,4-dione derivatives are a class of drugs that act as insulin sensitizers by activating peroxisome proliferator-activated receptor-gamma (PPAR-γ), a nuclear receptor that regulates glucose and lipid metabolism. The results of this study suggest that thiazolidine-2,4-dione derivatives may be a promising treatment option for T2DM by improving glycemic control, lipid metabolism, and renal and hepatic function.

Biological, toxicological and molecular docking evaluations of isoxazoline-thiazolidine-2,4-dione analogues as new class of anti-hyperglycemic agents.

In this work, three isoxazoline-thiazolidine-2,4-dione derivatives were synthesized and characterized by FT-IR, 1H-NMR, 13C-NMR and ESI-MS spectrometry. All compounds have been investigated for their α-amylase and α-glucosidase inhibitory activities. In vitro enzymatic evaluation revealed that all compounds were inhibitory potent against α-glucosidase with IC50 values varied from 40.67 ± 1.81 to 92.54 ± 0.43 µM, and α-amylase with IC50 in the range of 07.01 ± 0.02 to 75.10 ± 1.06 µM. One of the tested compounds were found to be more potent inhibitor compared to other compounds and standard drug Acarbose (IC50 glucosidase= 97.12 ± 0.35 µM and IC50 amylase= 2.97 ± 0.01 µM). All compounds were then evaluated for their acute toxicity in vivo and shown their safety at a high dose with LD > 2000mg/kg BW. A cell-based toxicity evaluation was performed to determine the safety of compounds on liver cells, using the MTT assay against HepG2 cells, and the results shown that all compounds have non-toxic impact against cell viability and proliferation compared to reference drug (Pioglitazone). Furthermore, the molecular homology analysis, SAR and the molecular binding properties of compound with the active site of α-amylase and α-glucosidase were confirmed through computational analysis. This study has identified the inhibitory potential of a new class of synthesized isoxazoline-thiazolidine-2,4-dione derivatives in controlling both hyperglycemia and type 2 diabetes mellitus without any hepatic toxicity.Communicated by Ramaswamy H. Sarma.

Synthesis, α-glucosidase and α-amylase inhibitory activities, acute toxicity and molecular docking studies of thiazolidine-2,4-diones derivatives.

In the present study, a series of thiazolidine-2,4-diones derivatives (3a-3e) and (4a-4e) were synthesized and characterized by 1H NMR, 13C NMR and ESI-MS spectrometry. All compounds were screened for their α-glucosidase and α-amylase inhibitory activities. In vitro biological investigations revealed that most of compounds were active against α-glucosidase with IC50 values in the range of 43.85 ± 1.06 to 380.10 ± 1.02 µM, and α-amylase with IC50 in the range of 18.19 ± 0.11 to 208.10 ± 1.80 µM. Some of the tested compounds were found to be more potent inhibitors than the clinical drug Acarbose (IC50glucosidase = 97.12 ± 0.35 µM and IC50amylase = 2.97 ± 0.004 µM). The lead compounds were evaluated for their acute toxicity on Swiss mice and found to be completely non-toxic with LD > 2000 mg/kg BW. Furthermore, the Structure-activity relationship (SAR) and the binding interactions of all compounds with the active site of α-glucosidase and α-amylase were confirmed through molecular docking and stabilizing energy calculations. This study has identified the inhibitory potential a new class of synthesized thiazolidine-2,4-diones in controlling both hyperglycemia and type 2 diabetes mellitus. Furthermore, the theoretical binding mode of the target molecules was evaluated by molecular docking studies against the 3D Crystal Structure of human pancreatic α-amylase (PDB ID: 1B2Y) and α-glucosidase (PDB ID: 3W37)Communicated by Ramaswamy H. Sarma.

Mineral and Phenolic Composition of Erodium guttatum Extracts and Investigation of Their Antioxidant Properties in Diabetic Mice.

Erodium guttatum is widely used in folk medicine in many countries to treat various ailments such as urinary inflammation, diabetes, constipation, and eczema. The aim of this study is the determination of mineral and phenolic compounds of E. guttatum extracts as well as the investigation of their antidiabetic and antioxidant properties. The mineral composition was determined by the methods of inductively coupled plasma atomic emission spectroscopy analysis. Phytochemical contents of total polyphenols, total flavonoids, and catechic tannins were estimated by colorimetric dosages. The phenolic composition was identified by high-resolution mass spectrometry (HRMS) analysis. The antioxidant activity of E. guttatum extracts was measured in vitro by five methods (DPPH, ABTS, FRAP, H2O2, and xanthine oxidase) and in vivo by assaying the malondialdehyde marker (MDA), superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH). The obtained results showed that the root plant material is rich in minerals such as k, Ca, and Mg. The methanolic extract of E. guttatum is the richest in polyphenols (389.20 ± 1.55 mg EAG/gE), tannins (289.70 ± 3.57 mg EC/gE), and flavonoids (432.5 ± 3.21 mg ER/gE). Concerning the ESI-HRMS analysis, it showed the presence of numerous bioactive compounds, including shikimic acid, rottlerine, gallic acid, and vanillic acid. Moreover, the aqueous and alcoholic extracts of E. guttatum exhibited antiradical and antioxidant activity in five tests used, with the best effect of the methanolic extract. Moreover, findings showed that in vivo investigations confirmed those obtained in vitro. On the other hand, E. guttatum showed important antidiabetic effects in vivo. Indeed, diabetic mice treated with extracts of E. guttatum were able to significantly reduce MDA levels and increase the secretion of enzymatic and nonenzymatic antioxidants (SOD, CAT, and GSH, respectively). However, the antioxidant activity of the extracts might be attributed to the abundance of bioactive molecules; as results, this work serves as a foundation for additional pharmacological research.

Chemical Profile, Antibacterial and Antioxidant Potential of Zingiber officinale Roscoe and Elettaria cardamomum (L.) Maton Essential Oils and Extracts.

The aim of this work was to study the chemical composition of the essential oil extracted from ginger rhizomes (Zingiber officinale Roscoe) and cardamom seeds (Elettaria cardamomum (L.) Maton). Using gas chromatography coupled with mass spectrometry (GC/MS), a total of 43 compounds were identified in ginger essential oil and 17 compounds in cardamom. The most abundant components, respectively, were zingiberene (22.18%) and 1.8-cinéol (43.47%). Essential oils, methanol, ethanol and chloroform extracts for both plants were tested against nine bacteria and yeast. The highest sensitivity was noticed against Staphylococcus aureus with a 25 mm inhibition zone. The antioxidant potency of both oils and extracts were measured using DPPH (1,1-diphenyl-2-picryl hydrazyl) free radical scavenging and the ferric reducing power (FRP) method; the ethanolic extract of cardamom fruits exhibited the best results for both tests, with an IC 50 = 0.423 ± 0.015 mg/mL and 95.03 ± 0.076 FRP mg AAE/g.

Solvent induced supramolecular polymorphism in Cu(II) coordination complex built from 1,2,4-triazolo[1,5-a]pyrimidine: Crystal structures and anti-oxidant activity.

Two Cu(II) coordination complexes, C1 and C2 of the formula [Cu(4)2(H2O)2], have been prepared by reaction between CuCl2·2H2O and 7-ethoxycarbonylmethyl-5-methyl-1,2,4[1,5-a]pyrimidine (L) in a 1:2 M:L molar ratio. The L molecule decomposes during the reaction process into 7-carboxy-5-methyl-[1,2,4]-triazolo[1,5-a]pyrimidine (4) through an intermediate, ethyl 2,2-dihydroxy-2-(5-methyl-[1,2,4]triazolo[1,5-a]pyrimidin-7-yl)acetate (5), which has been isolated and its crystal structure determined by X-ray diffraction. The X-ray analysis of the single crystals of [Cu(4)2(H2O)2] obtained from the slow evaporation of EtOH and MeOH, separately, revealed the formation of "solvent induced" polymorphs C1 and C2, respectively. The primary supramolecular synthon for C1 and C2 are six membered ring, and square shaped hydrogen bonded architecture, respectively. The self-assembly of such synthons resulted in a two dimensional hydrogen bonded sheet supported by OH⋯O interactions. In addition, the antioxidant properties of the ligands and its complexes were evaluated in vitro using 1,1-diphenyl-2-picrylhydrazyl acid, 2,2'-azino-bis (3-ethylbenzothiazoline-6 sulfonic acid radical scavenging methods and ferric reducing antioxidant power.

Evaluation of In Vitro Antioxidant and Antidiabetic Activities of Aristolochia longa Extracts.

Oxidative stress plays a major role in diabetic physiopathology; hence, the interest of using natural antioxidants as therapeutic tools exists. The aim of this study was the evaluation of in vitro antioxidant activity and inhibitory potential of organic extracts from Aristolochia longa roots against key enzymes linked to hyperglycemia. Antioxidant activity was performed using 2,2'-diphenyl-1-picrylhydrazyl (DPPH) and 2,2-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) radicals and ferric reducing/antioxidant power (FRAP) methods. The α-Glucosidase and ß-Galactosidase inhibitory activities were investigated using an in vitro model. Moreover, phytochemical analysis of tested extracts was carried out. The aqueous fraction of this herb exhibited the highest antioxidant activity for both DPPH and ABTS methods, IC50=125.40±2.40 µg/mL and IC50=65.23±2.49 µg/mL, respectively. However, the ethyl acetate fraction possessed the strongest inhibitory effect towards α-Glucosidase (IC50=1.112±0.026 mg/mL). Furthermore, the result showed high levels of phenolic content. The results showed that this plant could be a significant source of medically important natural compounds.

Novel Co(II) and Cu(II) coordination complexes constructed from pyrazole-acetamide: Effect of hydrogen bonding on the self assembly process and antioxidant activity.

In the present study, two pyrazole-acetamide derivatives namely N­(2­aminophenyl)­2­(5­methyl­1H­pyrazol­3­yl) acetamide (L1) and (E)­N­(2­(1­(2­hydroxy­6­methyl­4­oxo­4H­pyran­3­yl)ethylideneamino)phenyl)­2­(5­methyl­1H­pyrazol­3­yl) acetamide (L2) have been synthesized and characterized by infrared spectrophotometry (IR), nuclear magnetic resonance spectroscopy (NMR) and electrospray ionization-mass spectrometry (ESI-MS). Two coordination complexes of L1 and L2, namely [Co(L1)2(EtOH)2]·Cl2 (1) and [Cu(L2)]·H2O (2), respectively have been synthesized and characterized by elemental analysis and spectroscopic studies. The solid state structure of these two complexes was established by single crystal X-ray crystallography. In complex 1, the amide O and pyrazole N atoms of two molecules of L1 take part in coordination with octahedral Co(II) ions, the remaining two coordination sites being occupied by two EtOH molecules leading to a N2O4 coordination environment. On the other hand, the imine N atoms, pyrazole N and O atoms of the 2­hydroxy­6­methyl­4H­pyran­4­one function present in L2 are involved in coordination with Cu(II) ions, resulting in a distorted square planar geometry displaying a N2O4 chromophore, in complex 2. The crystal packing analysis of 1 and 2, revealed 1D and 2D supramolecular architectures respectively, via various hydrogen bonding interactions, which are discussed in the present account. Furthermore, the antioxidant activity of the ligands and their complexes were determined in vitro by 1,1­diphenyl­2­picrylhydrazyl (DPPH), 2,2'­azino­bis(3­ethylbenzothiazoline­6­sulphonic acid (ABTS) and ferric reducing antioxidant power(FRAP), showing that the ligands L1 and L2 and complexes 1 and 2 present significant antioxidant activity.